PROJECT SUMMARY/ABSTRACT The proposed study will combine qualitative and ecological momentary assessment (EMA) methods to conduct an in-depth examination of polysubstance use among people who use illicit opioids at the person- and event-levels. The overarching purpose of the research is to better understand the motivations, contexts, timing and sequencing of polysubstance use and related implications for opioid overdose risk behavior. Nearly three-quarters of fatal opioid overdoses in 2016 involved additional drugs. Studies tend to measure polysubstance use in broad timeframes such as 6 months or 30 days, which misses potential variations in patterns of use and cannot shed light on how substances are timed or combined. In addition, drug use is episodic and informed by a variety of individual and situational factors. Although these factors are typically measured through their statistical associations with polysubstance use, a different approach?examining such factors in the proximate context of daily life?will enhance our understanding of polysubstance use in general and polysubstance-related overdose risk in particular. We propose to conduct an intensive, mixed- methods examination of polysubstance use in a community-based sample of people who use illicit opioids. We will work with the Drug, Set, and Setting framework to examine both person- and event-level drug use patterns, as well as set and setting characteristics, that influence polysubstance use. The Specific Aims are: Aim 1: To use formative qualitative methods to explore and identify ?set? and ?setting? influences on polysubstance use among people who use illicit opioids. Aim 2: To use EMA methods to investigate polysubstance use timing, sequencing and drug combinations at the person- and event-level among people who use illicit opioids. Aim 3: To combine EMA and qualitative methods to conduct an in-depth examination of how ?set? and ?setting? factors are associated with polysubstance use at the person- and event-levels, with special emphasis on risk behavior for overdose. The proposed research will be conducted in Oakland, CA, with a community-based sample in a predominantly African American urban neighborhood. The proposed study will generate rich multimethod findings regarding polysubstance use at the person and event levels. Findings about proximate patterns of polysubstance can inform the next generation of overdose prevention strategies, as well as contribute to a stronger understanding overall of polysubstance use for future investigations.